At the 2008 meeting of the American Society of Hematology, held in San Francisco in December, there were several oral presentations on progress in autologous stem cell transplantation for the treatment of patients with multiple myeloma.

Autologous stem cell transplantation is an important component of the treatment of younger, more fit patients with multiple myeloma. There has been significant progress in the development of more effective induction and maintenance regimens in conjunction with autologous stem cell transplantation with the development of new agents such as Revlimid® (lenalidomide) and Velcade® (bortezomib). Some of these studies were presented at ASH 2008.

University of Arkansas: Total Therapy 3 in Good-risk Patients Defined by Gene Profiling

Researchers from the University of Arkansas have reported a series of large consecutive Phase II studies including tandem autologous transplants for myeloma called Total Therapy 1, 2, and 3. Total Therapy 3 incorporated Velcade and Thalomid® (thalidomide) into the treatment regimen in 303 newly diagnosed patients with myeloma.  These authors reported that patients with low-risk disease -- as defined by gene profiling -- had a four-year overall survival of 84% and an event-free survival of 77%. Patients with high-risk disease had an overall survival of 43% and an event-free survival of 33%. Sixty-three percent of patients in the low risk-group achieved a complete response, which was maintained at four years in 90% of patients. Only 57% of bad-risk patients who achieved a complete response maintained it for four years. These data suggest that a strategy which includes tandem transplants is highly effective in good-risk patients but that more effective therapy needs to be devised for those with adverse gene profiling.

Impact of Velcade in the Transplant Regimen

Researchers from France reported the results of a Phase II study which evaluated the addition of Velcade to high-dose melphalan followed by autologous stem cell infusion in patients with newly diagnosed myeloma.  There were 57 patients in this study, and induction was carried out with either VAD (vincristine, doxorubicin and dexamethasone) or Velcade and dexamethasone. The transplant regimen consisted of Velcade and melphalan. Prior to transplantation, 14% of patients had achieved a complete or very good partial response. Following transplantation with a Velcade/melphalan regimen, 36% of patients achieved a complete response and 25% achieved a very good partial response. These data also suggested superiority of Velcade/dexamethasone over VAD for induction therapy.

Velcade, Thalomid and Dexamethasone versus Thalomid and Dexamethasone

Researchers from Italy performed a Phase III randomized trial of induction therapy with Velcade, Thalomid and dexamethasone (VTD) versus Thalomid and dexamethasone (TD) in patients with newly diagnosed myeloma scheduled to receive tandem autologous stem cell transplants.  The following table summarizes the main findings of this randomized trial:

These authors concluded that Velcade in the induction regimen had a significant effect on the results of autologous stem cell transplantation.

Velcade, Doxorubicin and Dexamethasone Induction and Reduced-intensity Autografts in Elderly Patients

Italian researchers presented the results of a study of induction therapy with Velcade, doxorubicin and dexamethasone prior to planned reduced-intensity autologous stem cell transplants in elderly patients with newly diagnosed myeloma.  This study included over 100 patients aged 65-75 years with newly diagnosed myeloma. All received induction therapy with Velcade, dexamethasone and doxorubicin followed by tandem autologous stem cell transplants with 100 mg/m2 of melphalan. Peripheral blood stem cells were harvested after Cytoxan® (cyclophosphamide) and Neupogen® (figrastim). Revlimid® (lenalidomide) was given after recovery from tandem autologous transplants. After induction therapy, 94% of patients had at least a partial response. At least a very good partial response was observed in 59% and 13% had a compete response. After tandem autologous transplants, 41% of patients had a complete remission and, after Revlimid consolidation/maintenance, the complete remission rate was 53%. One-year survival was 92%. These authors concluded that Velcade, doxorubicin and dexamethasone was a very effective induction regimen which allowed the collection of autologous stem cells.

Similar Outcomes Following Transplantation for African Americans and Whites

African Americans have much higher myeloma incidence and mortality than Whites. African Americans are also 50% less likely to undergo an autologous stem cell transplant for myeloma compared to their White counterparts. At ASH 2008, researchers affiliated with the Center for International Blood and Marrow Transplantation Research reported that outcomes of African Americans undergoing stem cell transplantation were similar to those observed for comparable White patients with myeloma.  In this study, the outcomes of 303 African Americans were compared to the outcomes of 1,892 White patients receiving transplants for myeloma. African American patients were younger, had better performance scores, and had higher rates of hypertension, diabetes, and obesity.. Transplants for African Americans were performed later in their disease course than Whites. They also observed that the percentage of African Americans undergoing transplantation increased from 7% in 1995 to 17% in 2004. There were no differences in overall survival, relapse rate, or non-relapse mortality between African-Americans and Whites. These data suggest that African Americans could benefit just as much as Whites from a transplant for myeloma if they were offered this therapy.

These data are similar to those recently reported from the Walter Reed Army Medical Center where African Americans with equal access to medical care presented with similar stages of myeloma as Whites.  They also reported that the outcomes of transplantation for myeloma were identical to those achieved in the White population with myeloma. Thus, clinicians should be aware that in the Unites States, African Americans are receiving less intensive therapy with autologous transplantation for myeloma than their White counterparts despite the fact that myeloma is a much more common disease in this group and the results of transplantation are similar.
In summary; these data suggest that the addition of newer drugs to upfront treatment of newly diagnosed patients with myeloma has improved the results of autologous stem cell transplantation.

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